Separation of Uranium and Thorium for <sup>230</sup>Th-U Dating of Submarine Hydrothermal Sulfides

The age of a submarine hydrothermal sulfide is a significant index for estimating the size of hydrothermal ore deposits. Uranium and thorium isotopes in ...

Imaging Integrin Tension and Cellular Force at Submicron Resolution with an Integrative Tension Sensor

Molecular tension transmitted by integrin-ligand bonds is the fundamental mechanical signal in the integrin pathway that plays significant roles in many ...

Chinese Academy of Sciences

Iowa State University

Forces transmitted by integrins regulate many important cellular functions. Previously, we developed tension gauge tether (TGT) as a molecular force sensor and determined the threshold tension across a single integrin-ligand bond, termed integrin tension, required for initial cell adhesion. Here, we used fluorescently labeled TGTs to study the magnitude and spatial distribution of integrin tension on the cell-substratum interface. We observed two distinct levels of integrin tension. A >54 pN molecular tension is transmitted by clustered integrins in motile focal adhesions (FAs) and such force is generated by actomyosin, whereas the previously reported ∼40 pN integrin tension is transmitted by integrins before FA formation and is independent of actomyosin. We then studied FA motility using a TGT-coated surface as a fluorescent canvas, which records the history of integrin force activity. Our data suggest that the region of the strongest integrin force overlaps with the center of a motile FA within 0.2 μm resolution. We also found that FAs move in pairs and that the asymmetry in the motility of an FA pair is dependent on the initial FA locations on the cell-substratum interface. 

Integrin Molecular Tension within Motile Focal Adhesions.

Integrin-transmitted cellular forces are critical for platelet adhesion, activation, aggregation and contraction during hemostasis and thrombosis. Measuring and mapping single platelet forces are desired in both research and clinical applications. Conventional force-to-strain based cell traction force microscopies have low resolution which is not ideal for cellular force mapping in small platelets. To enable platelet force mapping with submicron resolution, we developed a force-activatable biosensor named integrative tension sensor (ITS) which directly converts molecular tensions to fluorescent signals, therefore enabling cellular force mapping directly by fluorescence imaging. With ITS, we mapped cellular forces in single platelets at 0.4µm resolution. We found that platelet force distribution has strong polarization which is sensitive to treatment with the anti-platelet drug tirofiban, suggesting that the ITS force map can report anti-platelet drug efficacy. The ITS also calibrated integrin molecular tensions in platelets and revealed two distinct tension levels: 12-54 piconewton (nominal values) tensions generated during platelet adhesion and tensions above 54 piconewton generated during platelet contraction. Overall, the ITS is a powerful biosensor for the study of platelet mechanobiology, and holds great potential in antithrombotic drug development and assessing platelet activity in health and disease.

Force-activatable biosensor enables single platelet force mapping directly by fluorescence imaging.

Rapid cell migration requires efficient rear de-adhesion. It remains undetermined whether cells mechanically detach or biochemically disassemble integrin-mediated rear adhesion sites in highly motile cells such as keratocytes. Using molecular tension sensor, we calibrated and mapped integrin tension in migrating keratocytes. Our experiments revealed that high-level integrin tension abbreviated as HIT, in the range of 50-100 pN (piconewton) and capable of rupturing integrin-ligand bonds, is exclusively and narrowly generated at cell rear margin during cell migration. Co-imaging of HIT and focal adhesions (FAs) shows that HIT is produced to mechanically peel off FAs that lag behind, and HIT intensity is correlated with the local cell retraction rate. High-level molecular tension was also consistently generated at the cell margin during artificially induced cell front retraction and during keratocyte migration mediated by biotin-streptavidin bonds. Collectively, these experiments provide direct evidence showing that migrating keratocytes concentrate force at the cell rear margin to mediate rear de-adhesion.

Keratocytes Generate High Integrin Tension at the Trailing Edge to Mediate Rear De-adhesion during Rapid Cell Migration.

Gaseous TMO(CO) (TM = Sc, Y, La) complex cations prepared via laser vaporization were mass-selected and studied by infrared photodissociation spectroscopy in the C-O stretching frequency region. The structures and vibrational frequencies were calculated by density functional theory to support and interpret the experimental results. The saturated coordination number of CO ligands for ScO(CO), YO(CO) and LaO(CO) was demonstrated to be six, seven and nine, respectively, namely, the nominal 18-, 20- and 24-electron gaseous cation complexes were synthesized. Based on our analysis of the electronic structure, the YO(CO) complex also obeys the 18-electron rule, since one of the occupied valence molecular orbitals is formed only by ligand orbitals. The contribution of 4f orbitals in LaO(CO) accounts for its high coordination number with a 24-electron valence shell.

Infrared photodissociation spectroscopic investigation of TMO(CO) (TM = Sc, Y, La): testing the 18-electron rule.

Polyprodrug nanoparticles have been employed recently for safer and more effective cancer treatment. However, it remains a challenge to elucidate how and when the polyprodrug nanoparticles are dissociated and activated to release active drugs in cancer cells. Herein, a visible light-activatable Pt(IV) prodrug and an aggregation-induced emission luminogen (AIEgen) were copolymerized and embedded in the main chain of PtAIECP, and the chemotherapeutic doxorubicin (DOX) was subsequently encapsulated in the nanoparticles self-assembled by PtAIECP (PtAIECP@DOX NP). PtAIECP@DOX NP enabled the monitoring of both the light-activation of Pt(IV) prodrug to active Pt(II) and release of encapsulated DOX intracellularly through the fluorescence "turn-on" in the course of visible-light-induced polymer-main-chain cleavage and self-assembled structure dissociation in vitro and ex vivo. The synergistic anticancer efficacy of the activated Pt(II) drug and DOX in PtAIECP@DOX NP was also investigated in vitro and in vivo. The implementation of polyprodrug and AIE combination strategy empowered dual drug release and monitoring, which could be further used to guide the temporal and spatial control of light irradiation to maximize therapeutic efficiency, and will inspire other combinational bioimaging and therapy strategies.

Light-Activatable Prodrug and AIEgen Copolymer Nanoparticle for Dual-Drug Monitoring and Combination Therapy.

A sulfonylation reaction of 4-substituted Hantzsch esters, DABCO·(SO2)2, and electron-deficient alkenes at room temperature in the presence of photoredox catalysis under visible light irradiation is described. Not only (E)-chalcones but also (vinylsulfonyl)benzene and 2-vinylpyridine are all suitable substrates in the transformation. This sulfonylation reaction under mild conditions shows a broad substrate scope with a good functional group compatibility. A plausible mechanism is proposed, which shows that the 4-substituted Hantzsch esters would be radical reservoirs under photoredox catalysis. The alkyl radical generated in situ from the 4-substituted Hantzsch ester would be trapped by sulfur dioxide to produce an alkylsulfonyl radical, which would then undergo further transformation leading to the final outcome.

Xuefeng Wang

Key Laboratory of Cenozoic Geology and Environment,
Institute of Geology and Geophysics,
Institutions of Earth Science,
Key Laboratory of Cenozoic Geology and Environment, Institute of Geology and Geophysics

Chinese Academy of Sciences

Separation of Uranium and Thorium for ²³⁰Th-U Dating of Submarine Hydrothermal Sulfides

Imaging Integrin Tension and Cellular Force at Submicron Resolution with an Integrative Tension Sensor

Xuefeng Wang

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Key Laboratory of Cenozoic Geology and Environment,Institute of Geology and Geophysics,Institutions of Earth Science,Key Laboratory of Cenozoic Geology and Environment, Institute of Geology and Geophysics

Chinese Academy of Sciences

Separation of Uranium and Thorium for 230Th-U Dating of Submarine Hydrothermal Sulfides

Imaging Integrin Tension and Cellular Force at Submicron Resolution with an Integrative Tension Sensor

Key Laboratory of Cenozoic Geology and Environment,
Institute of Geology and Geophysics,
Institutions of Earth Science,
Key Laboratory of Cenozoic Geology and Environment, Institute of Geology and Geophysics

Separation of Uranium and Thorium for ²³⁰Th-U Dating of Submarine Hydrothermal Sulfides